Dynamic protein biosynthesis via an integrated cell-on-a-chip platform device

使用生物技术方法在活的微生物中生产目标蛋白可能是费力的，并且与“活的”生化工厂相关的限制被证明是许多生物制造过程中的瓶颈。在这个项目中，我们的目标是通过开发一种活细胞的微流体模拟：芯片上的细胞，来开发基础技术来补救这一问题。我们的主张是，无细胞芯片实验室设备有潜力充当强大的微反应器，其中合成微室可以被设计和调整为以集成的方式工作，以执行特定的生物输出，包括基因表达，蛋白质合成，翻译后修饰和能量产生。这些特征都是整合的生物输出，最终可以使细胞-细胞信号传导导致细胞分化和更高阶的生物实体。在这个项目中，我们的目标是利用多学科的方法来实现这种芯片上的细胞设备，这些设备具有通过微流体阀连接的隔间细胞器样环境。该项目的最终目标是创建一个微型合成细胞芯片，用于动态和精确的蛋白质合成和生物过程工程。表达系统的小型化可以提高生产能力，也提供了一种新的制造工艺，可以带来可观的时空产量和较短的开发时间。它将对生物制药市场及其他领域产生改变游戏规则的影响，也将作为探索细胞生物学基础规则的平台。

Producing a target protein in living microorganisms using biotechnological approaches can be laborious, and limitations associated with 'living' biochemical factories are proving to be bottlenecks in many bio-manufacturing processes. In this project we aim to develop the underlying technologies to remedy this, by developing a microfluidic analogue of a living cell: a cell-on-chip. Our proposition is that cell-free lab-on-a-chip devices have the potential to act as robust microreactors where synthetic microcompartments can be designed and tuned to work in an integrated manner, in order to perform specific biological outputs including gene expression, protein synthesis, post-translational modifications and energy generation. These features are all integrated biological outputs that can eventually enable cell-cell signalling leading to cell differentiation and higher-order biological entities.In this project, we aim to utilise a multidisciplinary approach to realise such cell-on-a-chip devices with compartmentalised organelle-like environments that are connected via microfluidic valves. The final goal of this project is to create a microscale synthetic cell-on-chip for dynamic and precision protein synthesis and bioprocess engineering. The miniaturisation of expression systems can enhance production capacity and also offer a novel manufacturing process that can lead to substantial space-time yields and short development times. It will have game-changing implications for the biopharmaceutical market and beyond, and will also serve as platform to explore the rules underpinning cell biology.